An object of the present invention is to provide an improved method using nuclear magnetic resonance (NMR) for measuring the flow of fluid in a conduit, more particularly, to measure the flow of blood in a subject, either separately from or in the course of NMR tomographic examination.
The use of NMR to measure blood flow appears to be virtually a noninvasive technique and relies upon detecting the magnetization of hydrogen protons in the blood. Blood protons retain their magnetization direction for an average time of about 0.7 seconds, during which time a free induction decay (FID) signal corresponding to the magnetization can be detected and utilized in a variety of schemes to provide information about the velocity of the blood flow. A static, homogenous magnetic field is established in the region of interest and a radio frequency (R.F.) pulse is applied having a frequency equal to about the Larmor frequency of the paramagnetic fluid. The Larmor frequency is that frequency at which the vectors of the magnetic moments of the nuclei freely precess in the magnetic field. The theoretical tracking time for the FID signal is equivalent to T.sub.1 the classical relaxation time, i.e., the time during which the protons recover from the induced magnetization to the static magnetization. However, the decay of the FID signal is limited by other factors. It is dependent upon the relaxation time constant T.sub.2 (a constant that is a property of the fluid resulting in nonuniformity of the precessing protons and affecting the total magnetic moment), the magnetic field gradient, inhomogeneity of the static magnetic field, the fluid velocity and the length of the receiver coil. During the course of decay of the FID signal, one can apply a train of 180.degree. pulses to cause the precessing protons to "flip", yielding successive spin echo pulses which decrease in amplitude.
A review of blood flow measurement in the context of NMR imaging is contained in a paper by Singer: "Blood Flow Measurements by NMR of the Intact Body", IEEE Trans. on Nuclear Science (1980), 27:1245-1249. He describes a pulsed NMR experiment for velocity measurement of flowing fluids in which an R.F. pulse is applied in the presence or absence of a static magnetic field gradient. The received signal can be a FID signal or spin echoes can be measured if a suitable series of R.F. pulses is applied. In a paper by Grover and Singer: "NMR Spin-Echo Flow Measurements", J. Applied Phys. (1971), 42:938-940, a magnetic field gradient was applied in the direction of fluid flow with an R.F. pulse train 90.degree. - t - 180.degree.. where t is the time between the R.F. pulses. The amplitudes of the resulting spin echoes were measured as a function of t and the velocity distribution function derived from this information.
Garroway, in "Velocity Measurements in Flowing Fluids by NMR", J. Phys. D: Applied Phys. (1974), 7:L159-L163 suggested two methods for velocity measurement. He applied the magnetic field gradient perpendicular to the flow with a 90.degree. - t - 90.degree. R.F. pulse sequence. He measured the FID signal after the second pulse and showed that information on the spatial velocity profile can be obtained. His second method was similar to that of Grover and Singer. He applied the magnetic field gradient in the direction of flow and a (90.sub.0 - (t) - 90.sub.90) R.F. pulse sequence. Information on the flow of velocity distribution was obtained from the amplitudes of the spin echoes.
In a paper by Hemminga et al: "The Study of Flow by Pulsed Nuclear Magnetic Resonance. I. Measurement of Flow Rates in the Presence of a Stationery Phase Using a Difference Method", J. Magnetic Resonance (1977), 27:359-370, a Carr-Purcell-Meiboom-Gill (CPMG) pulse sequence to generate spin echoes was used in the absence of magnetic field gradients and the mean velocities were measured from the amplitude of the spin echos. In a subsequent paper by Hemminga: "The Study of Flow by Pulsed Nuclear Magnetic Resonance. II. Measurement of Flow Velocities Using a Repetitive Pulsed Method", J. Magnetic Resonance (1980), 37: 1-16, R.F. pulsed sequences were used in the presence of magnetic field gradients in the direction of flow. Velocity measurements were made using the amplitudes of the spin echoes.
Other methods for utilizing signals obtained during decay of the nuclear magnetic resonance of test fluid have been proposed. In Vander Hayden, U.S. Pat. No. 3,559,044, NMR is used to tag and detect a bolus to measure fluid flow. A tagging pulse is generated for each tagged bolus detected by a receiver coil, the period between successive tagging pulses defining a constant quantity of fluid passing through the conduit so that the number of pulses indicate the quantity of fluid flowing into the conduit. In Vander Hayden et al, U.S. Pat. No. 3,551,794, a signal responsive to the amplitude of the net magnetization of the fluid is used to measure flow, feedback being used to maintain a constant phase difference between the oscillators signal and the output signal. In Genthe et al Pat. No. 3,419,793 the number of pulses occurring in unit time is measured and is taken as proportional to the average fluid velocity. In Singer U.S. Pat. No. 3,191,119 a time-of-flight method is described in which the time elapsed between application of the excitation pulse and its detection is divided by the distance between the point of excitation and the point of detection to provide the flow rate.
A distinct drawback to all the foregoing methods of fluid velocity measurement is that they yield only the average velocity of the fluid. While such information is quite adequate for uniform or static systems, such as pipelines, and gives desirable information about the flow of blood, nevertheless average flow velocity does not adequately describe the physical conditions of the arteries and veins in the human body. For example, local variations in flow such as from artery blockages, from cholesterol buildup, the loss of elasticity and the like, and temporal variations from pulsations cannot be readily discerned using average velocity.
Furthermore, in any tubular vessel there is a spatial distribution between velocity along the inner surface of the walls and in the center of the vessel. Determining the spatial distribution of fluid velocity can yield important information as to the nature of the fluid flow, for example whether it is parabolic in shape, indicating laminar flow or nonparabolic, indicating turbulent flow. Because investigators have suspected there may be a link between turbulent arterial flow and artherogenesis, the matter has assumed a high degree of clinical interest. It would therefore be desirable to obtain not only information about the velocity of blood flowing in an artery or vein, but also information as to the velocity distribution as the blood progresses through the vessel.
In accordance with the present invention one readily obtains such information by measuring the instantaneous frequency of the nuclear magnetic resonance, either of the FID signal or of the spin echo signal, and deriving velocity information from the rate of change of the mean instantaneous frequency. Selection of the FID signal or spin echo pulse is governed by a feedback loop which monitors the velocity of the fluid and generates either signal depending upon the fluid velocity and/or decay of the FID signal. In addition, R.F. pulses are applied to suitable static axial magnetic gradients to obtain flow measurement from within a specific volume.
It will be appreciated that the methods provided herein can be used in fields other than measurement of the flow of blood in an artery or vein. More broadly, a method is provided for measuring the flow of fluid in a conduit, the atomic nuclei of at least one component of the fluid displaying a nuclear magnetic moment and angular momentum. As an initial step, a first, static, substantially homogenous axial magnetic field is established within the conduit and a magnetic field gradient is applied along the direction of flow of the fluid sufficient to induce nuclear paramagnetization in the fluid. An R.F. pulse having a frequency equal to the Larmor precession frequency of the nuclei of the element at the field intensity of the magnetic field is applied to a region within a conduit so as to alter the nuclear magnetization within a bolus of the fluid, thereby tagging the bolus with respect to fluid preceding and following the bolus. The frequency of nuclear magnetic resonance of the atomic nuclei of the element in the bolus, whether it be FID or spin echo, is measured over predetermined periods of time to obtain for each period of time the mean instantaneous frequency of the nuclear magnetic resonance. Velocity of the fluid is then derived from the rate of change of the mean instantaneous frequency.
In a particular implementation, a narrow band 90.degree. R.F. pulse is applied in the presence of G.sub.y. G.sub.y is the magnetic field gradient in the desired direction of the flow measurement. An appropriate gradient reversal of G.sub.y is then necessary for echo formation. This is followed by switching the field gradient along an orthogonal z-axis (G.sub.z) and applying a selective, narrow band 180.degree. pulse after time t.sub.1/2. After another time t.sub.1/2 the field gradient is switched along the x-axis (G.sub.x) and a selective, narrow band 180.degree. pulse is applied after time t.sub.2/2. Then, after a delay of t.sub.2/2 the field gradient is switched back to G.sub.y and FID and spin echoes can be measured for velocity determination. In this manner, the nuclear magnetization is altered within a selected volume of the fluid, thereby tagging that volume with respect to the fluid preceding and following the volume.
Initially, a 90.degree. R.F. pulse is applied to generate a FID signal, but because of the decay of the FID signal, the velocity information can only be obtained for some finite time and then a fresh R.F. pulse, selected to generate a FID signal, must be applied, i.e., a new 90.degree. R.F. pulse. Such a new pulse would be effective only if the magnetization at the selected region has reached the static equilibrium value. If the velocity of the fluid is sufficiently high then new material will have moved within the receiver coil and another 90.degree. R.F. pulse can be applied. However, if the velocity is low a new FID signal cannot be generated because the protons have not reached static magnetization. In accordance with a further embodiment of this invention, at that time, as long as there has not been full T.sub.2 decay, a series of 180.degree. R.F. pulses can be applied to generate a train of spin echo signals. On the other hand, if the FID signal has decayed due to true T.sub.2, then one would have to wait for a period of time, depending on T.sub.1 until the next 90.degree. R.F. pulse can be applied to generate a new FID signal. In accordance with a still further embodiment of the present invention, a method utilizing computerized feedback is provided to analyze the instantaneous position of the selected sample and amplitude of the generated signal, and suitably control the timing and phase of the next pulse.
More particularly, when magnetization of the tagged fluid has not reached a static value (i.e., within a time less than the spin-lattice relaxation time) a series of steps is conducted in which 180.degree. radio frequency pulses are applied to generate spin echo signals which are monitored and measured to obtain periodic samples of their mean instantaneous frequency deriving the velocity of the fluid from the rate of change of the mean instantaneous frequency and determining as well the amplitude of the signal. When the maximum amplitude of the spin echo signal is less than a predetermined threshold level a determination is made as to whether sufficient fluid flow has occurred or sufficient time has passed to reinstitute a 90.degree. R.F. pulse to generate another FID signal.
Accordingly, the present invention incorporates several improvements in the utilization of nuclear magnetic resonance to measure the flow of a fluid. One improvement of the FID or spin echo signals and deriving the velocity of the fluid from the rate of change of the mean instantaneous frequency. Another improvement is feedback of the timing and selection of the R.F. pulse to generate a series of spin echo signals alternating with FID signals. A still further improvement is the utilization, in conjunction with the measurement of the mean instantaneous frequency, of a sequence of magnetic field gradients and radiofrequency pulses to define a selected volume from within which the frequency is measured.